Comprehension of cell mechanisms regulating specific globin-chain synthesis during mammalian ontogeny is a significant problem in basic biology. In addition to better understanding of these mechanisms might lead to the clinical goal of permitting Alpha-globin-gene expression to continue into adult life in individuals with sickle cell diseases and the Beta-thalassemias. Our recent demonstrations of adult globins in primitive erythroid cells and of embryonic globin synthesis in post-natal erythroid tissue suggest to us that a close analysis of mouse hemoglobin ontogeny could provide new information applicable to studies on factors controlling globin-gene expression. That is our first specific aim. Our second specific aim, the identification of the relative contributions of cell pre-programming and extra-cellular factors on hemoglobin ontogeny, chiefly exploits our ability to grow pure preparations of yolk-sac erythroid cells in long-term culture. We propose to perform tightly controlled experiments on hemoglobins synthesized in these cells which are actively undergoing extensive ontogenic transitions. Our third specific aim, a search for correlations between hormone-receptor ontogeny and hemoglobin ontogeny, departs from previous phenomenologic examinations of specific globin-chain synthesis and represents an attempt to elucidate mechanisms at the subcellular level. Here we will look in particular for the location(s) of specific binding sites in erythroid cells and their characteristics (affinity constants and numbers per site).